Novel roles of bovine milk-derived exosomes in skin antiaging.

BACKGROUND: Exosomes are small vesicles released from cells and are found in various mammalian biological fluids, such as bovine milk, which has been employed in skincare for many years, apart from its dairy applications. In addition, exosomes have been recognized as vehicles for intercellular communication. AIMS: In this study, we aimed to investigate the novel effects of bovine milk-derived exosomes (MK-Exo) on antiaging in human skin. METHODS: Initially, MK-Exo were co-cultured with keratinocytes and fibroblasts; subsequent analysis involved qPCR and western blotting to assess induced gene expression. Subsequently, MK-Exo were topically applied to the facial skin of 31 female volunteers twice daily for 28 days. The functions were evaluated after conducting safety assessments in vivo. RESULTS: Purified MK-Exo demonstrated the ability to be taken up directly by keratinocytes and fibroblasts in vitro, resulting in the upregulation of natural factors associated with skin moisturization, including filaggrin (FLG), aquaporin 3 (AQP3), and CD44 in keratinocytes, as well as hyaluronidase (HAS2) in fibroblasts. Concurrently, MK-Exo promoted fibroblast cell migration and restored the expression of type I and III collagen (Col I and Col III) following exposure to ultraviolet radiation. Furthermore, phototoxicity, photoallergy, repeated skin irritation, skin allergy, and patch tests confirmed the safety of MK-Exo for skin application. Finally, we elucidated the roles of MK-Exo in preserving moisture and reducing wrinkles in humans. CONCLUSION: Our findings unveil the novel contributions of MK-Exo to human skin aging, presenting a new avenue in the field of skincare.

Intraduodenal Delivery of Exosome-Loaded SARS-CoV-2 RBD mRNA Induces a Neutralizing Antibody Response in Mice.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has presented numerous challenges to global health. Vaccines, including lipid-based nanoparticle mRNA, inactivated virus, and recombined protein, have been used to prevent SARS-CoV-2 infections in clinics and have been immensely helpful in controlling the pandemic. Here, we present and assess an oral mRNA vaccine based on bovine-milk-derived exosomes (milk-exos), which encodes the SARS-CoV-2 receptor-binding domain (RBD) as an immunogen. The results indicate that RBD mRNA delivered by milk-derived exosomes can produce secreted RBD peptides in 293 cells in vitro and stimulates neutralizing antibodies against RBD in mice. These results indicate that SARS-CoV-2 RBD mRNA vaccine loading with bovine-milk-derived exosomes is an easy, cheap, and novel way to introduce immunity against SARS-CoV-2 in vivo. Additionally, it also can work as a new oral delivery system for mRNA.

High-throughput quantitation of serological ceramides/dihydroceramides by LC/MS/MS: Pregnancy baseline biomarkers and potential metabolic messengers.

Ceramides and dihydroceramides are sphingolipids that present in abundance at the cellular membrane of eukaryotes. Although their metabolic dysregulation has been implicated in many diseases, our knowledge about circulating ceramide changes during the pregnancy remains limited. In this study, we present the development and validation of a high-throughput liquid chromatography-tandem mass spectrometric method for simultaneous quantification of 16 ceramides and 10 dihydroceramides in human serum within 5 min. by using stable isotope-labeled ceramides as internal standards. This method employs a protein precipitation method for high throughput sample preparation, reverse phase isocratic elusion for chromatographic separation, and Multiple Reaction Monitoring for mass spectrometric detection. To qualify for clinical applications, our assay has been validated against the FDA guidelines for Lower Limit of Quantitation (1 nM), linearity (R2>0.99), precision (imprecision<15 %), accuracy (inaccuracy<15 %), extraction recovery (>90 %), stability (>85 %), and carryover (<0.01 %). With enhanced sensitivity and specificity from this method, we have, for the first time, determined the serological levels of ceramides and dihydroceramides to reveal unique temporal gestational patterns. Our approach could have value in providing insights into disorders of pregnancy.

A prospective study of serum metabolomic and lipidomic changes in myopic children and adolescents.

BACKGROUND: Myopia is a prevalent eye disorder, especially among children and adolescents in eastern Asian countries. Multiple measures have already been taken to prevent and treat myopia, including atropine and dopamine. However, the serum metabolic picture of myopia has not yet been studied as a whole and remains largely unclear. In this paper, a prospective and panoramic study was carried out to find out the whole serum metabolomic and lipidomic picture of myopia. METHODS: With untargeted mass spectrometry (MS), myopia among 211 children and adolescents was studied. The MS features were first grouped across the samples. Then, compound annotation was carried out based on these features. Finally, the metabolite features were mapped to pathways, whose biological functions in myopia were studied and discussed. RESULTS: A total of 275 metabolite features were derived from 92 aligned MS peak groups with significant fold changes, and then mapped to 33 pathways. By a comprehensive consideration of significance, fold change, importance score and appearance in different omics, 9 pathways were selected, and their biological functions were further analyzed. Among these selected pathways, 5 pathways were related with oxidative stress, a validated phenomenon during myopia development, while 5 pathways were related with dopamine receptor D2, whose molecular function in myopia treatment is not fully understood. A total of 177 metabolite features from 45 peak groups were related with the studied pathways. CONCLUSION: This prospective study shed light on the whole picture of metabolomic mechanism underlying myopia and provided guidance to further elucidation of compounds and pathways in this whole picture.